Magnetic resonance imaging (MRI) is the most sensitive radiologic modality in visualizing multiple sclerosis (MS) plaques. However, the monotonous appearance of many lesions limits the usefulness of a single MRI in distinguishing active lesions from inactive ones. The proposed longitudinal studies are designed to utilize state-of-the-art volumetric image analysis and image-guided in vivo proton magnetic resonance spectroscopy (MRS) in combination with the paramagnetic contrast agent gadolinium diethylentriaminepentaacetic acid (GdDTPA) for distinguishing different stages of MRI-defined and clinically correlated disease activity. Volumetric image analysis performed on dual echo thin slices (3 mm) with no interslice gap will allow quantitation of total lesion burden as well as volumes of individual plaques independent of small unavoidable errors in repositioning the patients on serial scans. The number and degree of enhancement of plaques will also be quantified using the image analysis. Multivoxel proton MRS will be performed at short-echo times to visualize lipids and other membrane breakdown products from the plaque-containing as well as adjacent-tissue with a volume resolution on the order of 2 cc. MRS data will be quantitatively analyzed to critically assess the role of lipids, N-acetyl aspartate (NAA) and other MR-visible neurochemicals in the characterization of MS plaques. Linked GdDTPA MRI and MRS should allow us to determine the MRS-defined changes in the neurochemicals in relation to acute changes in regional vascular permeability. Computed Relaxation images should allow the detection of plaques even when they are too small to be resolved on MRI or prior to GdDTPA enhancement. Many of the patients will be scanned at intervals of four weeks up to a period of six months. Magnetic resonance results will be correlated with clinical status. These multi-pronged MA studies should allow us to characterize and follow the evolution of MS plaques and improve our understanding of the pathophysiology of MS. A further significance of these studies is that they may enable us to follow objectively and quantitatively the efficacy of drugs in the treatment of MS.